Mucopolysaccharidosis VII, MPSVII

 

Gene: GUSB

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

German Shepherd mutation: Substitution, GUSB gene; c.497 G>A, p.(R166H)

Brazilian Terrier mutation: Substitution, GUSB gene; c.866 C>T, p.(P289L)

Medical system: Metabolic, lysosomal storage disease

Breeds: American Staffordshire Terrier/Amstaff, Brazilian Terrier, German Shepherd

Age of onset of symptoms: Around the age of 4 to 8 weeks

Mucopolysaccharidosis VII is a hereditary lysosomal storage disease.  There is a deficiency of the enzyme beta-glucuronidase, resulting in an accumulation of undigested glycosaminoglycans (GAGs) within cells.  GAGs are required for normal connective tissue functions, and cellular accumulation of GAGs will impair the normal growth of animals.  Affected puppies are active and have a good appetite but have marked growth retardation. They have big heads but a small muzzle; crooked shortened legs and swollen joints resulting in difficulty walking.  There is corneal opacity and there may be heart problems.  There is no treatment and puppies are most often euthanized for humanitarian reasons.

 

References:

OMIA link: [0667-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Peck SH, Lau YK, Kang JL, et al. (2021) Progression of vertebral bone disease in mucopolysaccharidosis VII dogs from birth to skeletal maturity. Mol Genet Metab 133(4) :378-385.  [pubmed/34154922]

Story BD, Miller ME, Bradbury AM, et al. (2020) Canine models of inherited musculoskeletal and neurodegenerative diseases. Front Vet Sci 7:80. [pubmed/32219101]

Hytönen MK, Arumilli M, Lappalainen AK, et al. (2012) A Novel GUSB Mutation in Brazilian Terriers with Severe Skeletal Abnormalities Defines the Disease as Mucopolysaccharidosis. PLoS One 7:e40281.  [pubmed/22815736]

Silverstein Dombrowski DC, Carmichael KP, Wang P, O’Malley TM, Haskins ME, Giger U. (2004) Mucopolysaccharidosis type VII in a German Shepherd dog. J Am Vet Med Assoc 224(4) :553-7, 532-3. [pubmed/14989549]

Ray J, Bouvet A, DeSanto C, Fyfe JC, et al. (1998) Cloning of the canine beta-glucuronidase cDNA, mutation identification in canine MPS VII, and retroviral vector-mediated correction of MPS VII cells. Genomics. 48(2):248-53. [pubmed/9521879]

Ray J, Haskin ME, Ray K. (1998) Molecular diagnostic tests for ascertainment of genotype at the mucopolysaccharidosis type VII locus in dogs. AJVR 59(9):1092-1095. [pubmed/9736382]

Haskins ME, Aguirre GD, Jezyk PF, et al. (1991) Mucopoysaccharidosis type VII (Sly Syndrome). Beta-glucuronidase-deficient mucopolysaccharidosis in the dog. Am J Pathol. 138(6):1553-5. [pubmed/1905109]